NCT03896152

Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

A Multi-center, Randomized, Open-label, Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria and Active Hemolysis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a Phase II randomized, open-label, multicenter, efficacy, safety, pharmacokinetic and pharmacodynamic study assessing four iptacopan doses in adult Paroxysmal nocturnal hemoglobinuria (PNH) patients with active hemolysis who were not on eculizumab or any other complement inhibitor less than 3 months prior to first iptacopan dose. Active hemolysis was defined by a lactate dehydrogenase (LDH) value ≥ 1.5 × ULN.

Detailed description

LNP023 is a novel oral small molecular weight compound, that inhibits alternative complement pathway (AP). Blockade of the AP with oral LNP023 has the potential to prevent both intra - and extravascular hemolysis. The total study duration from Screening until end of study (EOS) was approximately 28 months. This three-period study included: * Screening phase: of up to 8 weeks * Period 1: a 4-week treatment period of iptacopan at the first dose in the assigned sequence * Period 2: an 8-week treatment period at the second dose in the assigned sequence * Period 3: an approximate 2-year treatment extension period for patients who responded to iptacopan treatment * Taper down period of 2 weeks was applicable only for patients discontinuing iptacopan treatment (Week 13 for non-responders or Week 109 for responders who did not enter the rollover extension program (REP) (Study CLNP023C12001B / NCT04747613)). During this taper down period, patients were to receive 25 mg qd (once a day) of iptacopan for 7 days, followed by 10 mg qd for 7 additional days. * An EOS visit that took place 1 week after the last iptacopan administration for patients not joining the REP. For patients joining the REP, the last treatment visit was the EOS visit. * A safety follow-up call 30 days after the last administration of iptacopan was performed for patients not joining the REP. Patients were randomized to Sequence 1 or Sequence 2 in a 1:1 ratio. Sequence 1: Four weeks of treatment with iptacopan 25 mg bid (Twice daily) in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 100 mg bid (starting from Study Day 17). If LDH was not reduced by ≥ 40% from the mean of pretreatment values at Week 4 (Day 29), the iptacopan dose was to be up-titrated to 200 mg bid in Period 2 and Period 3 (starting from Study Day 30). In the approximate 2-year treatment extension (Period 3), patients maintained the same treatment regimen as used in Period 2. Sequence 2: Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3. If during Period 1, LDH was not reduced by ≥ 40% from the mean of pretreatment values by Week 2 (Day 15 study visit), the iptacopan dose was to be up-titrated to 200 mg bid (starting from Study Day 17). In the approximate 2-year treatment extension (Extension Period 3), patients remained on 200 mg bid. No further up-titration was possible

Conditions

• Paroxysmal Nocturnal Hemoglobinuria

Interventions

Type	Name	Description
DRUG	LNP023	approximately 2 year of Treatment with LNP023

Timeline

• Start date: 2019-04-05
• Primary completion: 2020-04-07
• Completion: 2022-02-09
• First posted: 2019-03-29
• Last updated: 2024-06-18
• Results posted: 2023-12-18

Locations

5 sites across 4 countries: Malaysia, Singapore, South Korea, Taiwan